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超灵敏响应的近红外荧光硝基还原酶探针,具有很强的肿瘤成像特异性,并能检测肿瘤细胞的侵袭性。

Ultra-sensitive responsive near-infrared fluorescent nitroreductase probe with strong specificity for imaging tumor and detecting the invasiveness of tumor cells.

机构信息

Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China.

School of Water Conservancy and Environment, University of Jinan, Jinan 250022, China.

出版信息

Spectrochim Acta A Mol Biomol Spectrosc. 2022 Mar 5;268:120634. doi: 10.1016/j.saa.2021.120634. Epub 2021 Nov 17.

DOI:10.1016/j.saa.2021.120634
PMID:34836811
Abstract

Hypoxia plays an important role in cancer progression, which is a characteristic feature of the tumor micro-environment and reflects the invasiveness of tumor cells. Nitroreductase (NTR) is overexpressed in hypoxic tumors, which making it an efficient target for detecting the hypoxic state in tumor. In this work, a new type of nitro-based fluorescent probe, named HNT-NTR, has been proposed, HNT-NTR could detect specifically and rapidly the NTR degree, which reflects the level of hypoxia in bidimensional (2D) tumor cells, three-dimensional (3D) tumor spheres and even the real tumors in vivo without biological toxicity. Most importantly, according to the research, HNT-NTR even could distinguish tumor cells from other normal cells in vivo and reflect the invasiveness of tumor cells by the near-infrared fluorescence intensity, which provides a new way of clinical pathologic diagnosis. All in all, HNT-NTR not only is proven to be an ideal probe for detecting solid tumors in vivo, but also has great potential to distinguish if cells are benign or malignant and even guide therapeutic applications in the clinic.

摘要

缺氧在癌症进展中起着重要作用,这是肿瘤微环境的一个特征,反映了肿瘤细胞的侵袭性。硝基还原酶(NTR)在缺氧肿瘤中过度表达,使其成为检测肿瘤缺氧状态的有效靶点。在这项工作中,提出了一种新型的硝基荧光探针,命名为 HNT-NTR。HNT-NTR 可以特异性和快速地检测 NTR 程度,反映二维(2D)肿瘤细胞、三维(3D)肿瘤球体甚至体内真实肿瘤的缺氧水平,而且没有生物毒性。最重要的是,根据研究,HNT-NTR 甚至可以在体内区分肿瘤细胞和其他正常细胞,并通过近红外荧光强度反映肿瘤细胞的侵袭性,这为临床病理诊断提供了一种新方法。总之,HNT-NTR 不仅被证明是一种理想的体内检测实体肿瘤的探针,而且具有很大的潜力来区分细胞是良性还是恶性,甚至可以指导临床治疗应用。

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